Dendritic cells ameliorate autoimmunity in the cns by controlling the homeostasis of PD-1 receptor+ regulatory T cells

Nir Yogev, Friederike Frommer, Dominika Lukas, Kordula Kautz-Neu, Khalad Karram, Daniele Ielo, Esther von Stebut, Hans Christian Probst, Maries van den Broek, Dieter Riethmacher, Tal Birnberg, Thomas Blank, Boris Reizis, Thomas Korn, Heinz Wiendl, Steffen Jung, Marco Prinz, Florian C. Kurschus, Ari Waisman

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c+ DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice.

Original languageEnglish
Pages (from-to)264-275
Number of pages12
JournalImmunity
Volume37
Issue number2
DOIs
Publication statusPublished - Aug 24 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Yogev, N., Frommer, F., Lukas, D., Kautz-Neu, K., Karram, K., Ielo, D., von Stebut, E., Probst, H. C., van den Broek, M., Riethmacher, D., Birnberg, T., Blank, T., Reizis, B., Korn, T., Wiendl, H., Jung, S., Prinz, M., Kurschus, F. C., & Waisman, A. (2012). Dendritic cells ameliorate autoimmunity in the cns by controlling the homeostasis of PD-1 receptor+ regulatory T cells. Immunity, 37(2), 264-275. https://doi.org/10.1016/j.immuni.2012.05.025